The efficacy of therapeutic polypeptides is often greatly limited by their intrinsic pharmacokinetic properties. For example, in the case of therapeutic antibodies, problems with tissue penetration, tissue residency and serum half-life are frequently reported. Improvements in the pharmacokinetic properties of a therapeutic polypeptide can result in improved efficacy and reduced dosing regimes. Current methods of modulating the pharmacokinetic properties of therapeutic polypeptides are typically limited to addressing the issue of serum half-life. Moreover these methods typically involve time consuming or non-specific chemical alteration of existing polypeptides.
Accordingly, there is a need in the art for improved methods of modulating the pharmacokinetic properties of therapeutic polypeptides that provide a rapid and specific means of amino acid modification, and that address pharmacokinetic parameters in addition to half-life.